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Physiological Reviews Jul 2022Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological... (Review)
Review
Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular, and genetic levels: the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis, and regeneration, and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.
Topics: Cell Lineage; Humans; Oral Health; Regeneration; Salivary Glands; Signal Transduction
PubMed: 35343828
DOI: 10.1152/physrev.00015.2021 -
Nature Reviews. Molecular Cell Biology Nov 2020Bone development occurs through a series of synchronous events that result in the formation of the body scaffold. The repair potential of bone and its surrounding... (Review)
Review
Bone development occurs through a series of synchronous events that result in the formation of the body scaffold. The repair potential of bone and its surrounding microenvironment - including inflammatory, endothelial and Schwann cells - persists throughout adulthood, enabling restoration of tissue to its homeostatic functional state. The isolation of a single skeletal stem cell population through cell surface markers and the development of single-cell technologies are enabling precise elucidation of cellular activity and fate during bone repair by providing key insights into the mechanisms that maintain and regenerate bone during homeostasis and repair. Increased understanding of bone development, as well as normal and aberrant bone repair, has important therapeutic implications for the treatment of bone disease and ageing-related degeneration.
Topics: Animals; Bone Development; Bone Diseases; Bone and Bones; Humans; Regeneration
PubMed: 32901139
DOI: 10.1038/s41580-020-00279-w -
Development (Cambridge, England) Sep 2019Tissue damage can resolve completely through healing and regeneration, or can produce permanent scarring and loss of function. The response to tissue damage varies... (Review)
Review
Tissue damage can resolve completely through healing and regeneration, or can produce permanent scarring and loss of function. The response to tissue damage varies across tissues and between species. Determining the natural mechanisms behind regeneration in model organisms that regenerate well can help us develop strategies for tissue recovery in species with poor regenerative capacity (such as humans). The zebrafish () is one of the most accessible vertebrate models to study regeneration. In this Primer, we highlight the tools available to study regeneration in the zebrafish, provide an overview of the mechanisms underlying regeneration in this system and discuss future perspectives for the field.
Topics: Animals; Drug Evaluation, Preclinical; Genetic Techniques; Humans; Models, Animal; Organogenesis; Regeneration; Zebrafish
PubMed: 31540899
DOI: 10.1242/dev.167692 -
The Journal of Investigative Dermatology Oct 2022Skin wounds in adult mammals typically heal with a fibrotic scar and fail to restore ectodermal appendages, such as hair follicles or adipose tissue. Intriguingly, new... (Review)
Review
Skin wounds in adult mammals typically heal with a fibrotic scar and fail to restore ectodermal appendages, such as hair follicles or adipose tissue. Intriguingly, new hair follicles regenerate in the center of large full-thickness wounds of mice in a process called wound-induced hair neogenesis (WIHN). WIHN is followed by neogenesis of dermal adipose tissue. Both neogenic events reactivate embryonic-like cellular and molecular programs. The WIHN model provides a platform for studying mammalian regeneration, and findings from this model could instruct future regenerative medicine interventions for treating wounds and alopecia. Since Ito et al. rediscovered WIHN 15 years ago, numerous investigators have worked on the WIHN model using varying wounding protocols and model interpretations. Because a variety of factors, including environmental variables and choice of mouse strains, can affect the outcomes of a WIHN study, the purpose of this article is to provide an overview of the experimental variables that impact WIHN so that experiments between laboratories can be compared in a meaningful manner.
Topics: Animals; Hair; Hair Follicle; Mammals; Mice; Mice, Inbred C57BL; Regeneration; Skin; Wound Healing
PubMed: 36153062
DOI: 10.1016/j.jid.2022.07.013 -
Neuron Aug 2022Injured neurons in the adult mammalian central nervous system often die and seldom regenerate axons. To uncover transcriptional pathways that could ameliorate these...
Injured neurons in the adult mammalian central nervous system often die and seldom regenerate axons. To uncover transcriptional pathways that could ameliorate these disappointing responses, we analyzed three interventions that increase survival and regeneration of mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC) injury, albeit not to a clinically useful extent. We assessed gene expression in each of 46 RGC types by single-cell transcriptomics following ONC and treatment. We also compared RGCs that regenerated with those that survived but did not regenerate. Each intervention enhanced survival of most RGC types, but type-independent axon regeneration required manipulation of multiple pathways. Distinct computational methods converged on separate sets of genes selectively expressed by RGCs likely to be dying, surviving, or regenerating. Overexpression of genes associated with the regeneration program enhanced both survival and axon regeneration in vivo, indicating that mechanistic analysis can be used to identify novel therapeutic strategies.
Topics: Animals; Axons; Cell Survival; Mammals; Mice; Nerve Regeneration; Optic Nerve Injuries; Retinal Ganglion Cells
PubMed: 35767994
DOI: 10.1016/j.neuron.2022.06.002 -
Nature Reviews. Cardiology Feb 2024Permanent fibrosis and chronic deterioration of heart function in patients after myocardial infarction present a major health-care burden worldwide. In contrast to the... (Review)
Review
Permanent fibrosis and chronic deterioration of heart function in patients after myocardial infarction present a major health-care burden worldwide. In contrast to the restricted potential for cellular and functional regeneration of the adult mammalian heart, a robust capacity for cardiac regeneration is seen during the neonatal period in mammals as well as in the adults of many fish and amphibian species. However, we lack a complete understanding as to why cardiac regeneration takes place more efficiently in some species than in others. The capacity of the heart to regenerate after injury is controlled by a complex network of cellular and molecular mechanisms that form a regulatory landscape, either permitting or restricting regeneration. In this Review, we provide an overview of the diverse array of vertebrates that have been studied for their cardiac regenerative potential and discuss differential heart regeneration outcomes in closely related species. Additionally, we summarize current knowledge about the core mechanisms that regulate cardiac regeneration across vertebrate species.
Topics: Animals; Infant, Newborn; Humans; Heart; Myocardial Infarction; Models, Animal; Regeneration; Cardiovascular Physiological Phenomena; Myocytes, Cardiac; Cell Proliferation; Mammals
PubMed: 37580429
DOI: 10.1038/s41569-023-00914-x -
Annual Review of Physiology Feb 2020Regenerative processes that maintain the function of the gastrointestinal (GI) epithelium are critical for health and survival of multicellular organisms. In insects and... (Review)
Review
Regenerative processes that maintain the function of the gastrointestinal (GI) epithelium are critical for health and survival of multicellular organisms. In insects and vertebrates, intestinal stem cells (ISCs) regenerate the GI epithelium. ISC function is regulated by intrinsic, local, and systemic stimuli to adjust regeneration to tissue demands. These control mechanisms decline with age, resulting in significant perturbation of intestinal homeostasis. Processes that lead to this decline have been explored intensively in in recent years and are now starting to be characterized in mammalian models. This review presents a model for age-related regenerative decline in the fly intestine and discusses recent findings that start to establish molecular mechanisms of age-related decline of mammalian ISC function.
Topics: Aging; Animals; Cellular Senescence; Epithelial Cells; Humans; Intestinal Mucosa; Intestines; Regeneration; Stem Cells
PubMed: 31610128
DOI: 10.1146/annurev-physiol-021119-034359 -
Journal of Endodontics Jan 2023The conventional treatment for irreversibly inflamed or necrotic teeth is root canal treatment or apexification. Regenerative endodontics aims to regenerate the damaged... (Review)
Review
INTRODUCTION
The conventional treatment for irreversibly inflamed or necrotic teeth is root canal treatment or apexification. Regenerative endodontics aims to regenerate the damaged "pulp-like" tissue, which can preserve the teeth' vitality and sensitivity while avoiding necrosis. The main clinical benefit is root maturation. The "pulp-like" tissue does not refer to regenerated pulp tissue with an odontoblastic layer or the formation of pulp-dentin complexes. The cell homing technique is built on endogenous stem cells and their capacity to regenerate tissue. Cell homing refers to endogenous cells' migration or infiltration into the cite when stimulated by physiochemical or biological stimuli or by passive flow with a blood clot from the apical tissue. Its Regenerative Endodontic Procedures success criteria are defined by the American Association of Endodontists. The purpose of this article is to provide an overview of vital pulp tissue and various strategies to promote regeneration of damaged pulp tissue. The cell homing technique will be reviewed through clinical trials.
METHODS
We performed a comprehensive literature review on a total of nine clinical trials of regenerative endodontics using the cell-homing technique based on three databases and duplicate manuscripts were removed.
RESULTS
Regenerative endodontics using the cell-homing technique shows promising results that can be translated into clinical practice. However, a favorable result was observed in immature teeth, and the results are contradictory in mature teeth.
CONCLUSION
Regeneration therapy is an attractive new alternative to conventional endodontic treatments. Preservation of vitality and continuation of root development in damaged teeth would be a clear advantage.
Topics: Humans; Regenerative Endodontics; Dental Pulp Necrosis; Tooth Apex; Apexification; Dental Pulp; Root Canal Therapy; Regeneration; Endodontics
PubMed: 36270575
DOI: 10.1016/j.joen.2022.09.008 -
Advanced Healthcare Materials Nov 2022Much effort has been made to generate human skin organ in the laboratory. Yet, the current models are limited due to the lack of many critical biological and structural... (Review)
Review
Much effort has been made to generate human skin organ in the laboratory. Yet, the current models are limited due to the lack of many critical biological and structural features of the skin. Importantly, these in vitro models lack appendages and fail to recapitulate the whole human skin construction. Thus, engineering a human skin with the capacity to generate all components, including appendages, is a major challenge. This review intends to provide an update on the recent efforts underway to regenerate appendage-bearing skin organs based on scaffold-free and scaffold-based bioengineering approaches. Although the mouse skin equivalents containing hair follicles, sebaceous glands, and sweat glands have been established in vitro, there has been limited success in humans. A combination of biofabricated matrices and cell aggregates, such as organoids, can pave the way for generating skin substitutes with human-like biological, structural, and physical features. Accordingly, the formation of human skin organoids and reconstruction of vascularized skin equipped with immune cells prompt calls for more scientific research. The generation of appendage-bearing skin substitutes can be applied in practice for wound healing, hair restoration, and scar treatment.
Topics: Mice; Animals; Humans; Skin; Hair Follicle; Skin, Artificial; Wound Healing; Regeneration
PubMed: 36063498
DOI: 10.1002/adhm.202201626 -
International Journal of Molecular... Oct 2020Central nervous system (CNS) injury, including stroke, spinal cord injury, and traumatic brain injury, causes severe neurological symptoms such as sensory and motor... (Review)
Review
Central nervous system (CNS) injury, including stroke, spinal cord injury, and traumatic brain injury, causes severe neurological symptoms such as sensory and motor deficits. Currently, there is no effective therapeutic method to restore neurological function because the adult CNS has limited capacity to regenerate after injury. Many efforts have been made to understand the molecular and cellular mechanisms underlying CNS regeneration and to establish novel therapeutic methods based on these mechanisms, with a variety of strategies including cell transplantation, modulation of cell intrinsic molecular mechanisms, and therapeutic targeting of the pathological nature of the extracellular environment in CNS injury. In this review, we will focus on the mechanisms that regulate CNS regeneration, highlighting the history, recent efforts, and questions left unanswered in this field.
Topics: Animals; Axons; Central Nervous System; Humans; Myelin Sheath; Nerve Regeneration; Remyelination
PubMed: 33143194
DOI: 10.3390/ijms21218116